The major goal of this application is to purchase a Gammacell 40 Exactor, a gamma irradiator, for use in irradiation of mice, cells, and tissue. The major users of the instrument are NIH funded investigators whose work is heavily dependent on the use of a gamma irradiator device. Major users projects included in this application cover a variety of disciplines, including: endothelial progenitor function and angiogenesis in mice and humanized mice; hematopoietic stem cell transplantation, differentiation, and leukemia development in mice; mouse models for investigating the regulation of iron homeostasis; oxidant stress in hematopoietic cell development in mice; humanized mouse models for hematopoietic stem cell anti-HIV-1 gene delivery and HIV-1 pathogenic studies; mouse models for cell transplantation and islet xenotransplantation; autoimmune disease models; breast cancer metastasis; preclinical studies using mouse models to evaluate the ability of activated protein C to reduce mortality caused by radiation DNA damage induced cell cycle check point control; and small interference RNA and ribozymes in treating HIV infection. We are requesting a state-of-the-art gamma irradiator that will allow us to continue currently funded studies and will accommodate anticipated increased demand for irradiator access that cannot be met by our current 27 year old Model 143-35 gamma irradiator due to limitations of capacity and degrading mechanical function due to advanced age. [unreadable] [unreadable] Objective: The long-term objective of this proposal is to provide researchers at The Department of Molecular and Experimental Medicine and The Scripps Research Institute a current generation gamma irradiator that provides humane, reliable, reproducible, and trouble free irradiation for the treatment of small animals. This instrument will also be used for treatment of cells and tissues. [unreadable] [unreadable] Relevance: Identified user groups are all involved in disease specific research that is highly relevant to human health, and receive support from several NIH institutes. The investigations span the research spectrum from insight into basic cellular and molecular mechanism to preclinical models.7. Project narrative: [unreadable] [unreadable] [unreadable]